Modern cardiovascular research relies on the mouse species for providing a model for human cardiovascular disease. A significant portion of basic cardiovascular research relates to the anatomic and physiological response of the heart to myocardial infarction (MI). There is a pressing need for improvements in noninvasive imaging methods for quantifying myocardial function with fine spatial and temporal resolution so as to differentiate wall function at the intramyocardial level and to characterize the precise location and nature of the "border zone" adjacent to the post MI necrotic tissue. The long term goals of the proposed work are to develop the instrumentation and techniques for investigating noninvasively the time evolution of the complex interactions between a coronary ischemic event and resulting measurable phenomena. The work encompasses 4D (3D + time) assessment of wall function (i.e. strain, contractile function) using a blend of new image processing techniques and mathematical model fitting. Additionally, we plan to map the presence of specific cell adhesion molecules (i.e., PECAM and selectin) that are presented on the endothelial surface following an ischemic event. Finally, we will test the hypothesis that inter-regional dyssynchrony post-MI (as detected by high-resolution ultrasound) will be reduced in inducible Nitric Oxide Synthase (iNOS) knock out (KO) mice. The Specific Aims are to: A.1 Develop instrumentation enabling fine spatial (<100 um) and temporal (8000 frame/s) resolution 3D tracking for assessing strain using orthogonal sets of acquired 2D data and 3D mathematical models of the murine heart, A.2 Develop an automated tissue analysis technique: "active trajectory field models" to recover 4D (3D + time) myocardial motion from echocardiographic imagery via a 4D myocardial deformation model, A.3 Develop methods for 3D mapping of the molecular markers of inflammation resulting from MI - specifically: Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM) and P/E Selectin, and A.4 Test the hypothesis that the cardiac dyssynchrony that develops late after MI in the remote LV will be markedly reduced in iNOS knock-out mice vs. wild-type mice. Broadly speaking, the proposed work involves developing improved techniques for mouse heart imaging that will facilitate more precise mouse-based heart disease research. The knowledge gained using experiments on mice may ultimately result in the improved management of human cardiovascular disease patients. PUBLIC HEALTH RELEVANCE: Cardiovascular research relies heavily on the mouse species for providing a model for human cardiovascular disease. A significant proportion of basic cardiovascular research relates to tracking the anatomic and physiological response of the heart muscle post myocardial infarction (MI). There is a pressing need for improvements in noninvasive imaging methods for quantifying myocardial function with fine spatial and temporal resolution so as to differentiate wall function at the intramyocardial level and to characterize the precise location and nature of the "border", or "at-risk", zone in vicinity of post MI necrotic tissue. The proposed work involves developing improved imaging techniques for mouse hearts that will facilitate more precise mouse-based heart disease research. The knowledge gained using experiments on mice may ultimately result in improved management of human cardiovascular disease patients. This knowledge may help direct the development of new drug therapies or medical devices related to heart health management.